Helix formation in preorganized β/γ-peptide foldamers: Hydrogen-bond analogy to the α-helix without α-amino acid residues

We report the first high-resolution structural data for the β/γ-peptide 13-helix (i,i+3 CO⋯HN H-bonds), a secondary structure that is formed by oligomers with a 1:1 alternation of β- and γ-amino acid residues. Our characterization includes both crystallophaphic and 2D NMR data. Previous studies suggested that β/γ-peptides constructed from conformationally flexible residues adopt a different helical secondary structure in solution. Our design features preorganized β- and γ-residues, which strongly promote 13-helical folding by the 1:1 β/γ backbone.